Saturday, February 06, 2010

Beautiful butterflies & localized adaptation   posted by Razib @ 2/06/2010 09:17:00 PM

Two new papers are out in PLoS Biology which make inferences about adaptation using butterfly species which exhibit Mullerian mimicry. I'll give the author summaries instead of the abstracts.

Genomic Hotspots for Adaptation: The Population Genetics of Mullerian Mimicry in the Heliconius melpomene Clade:
The diversity of wing patterns in Heliconius butterflies is a longstanding example of both Mullerian mimicry and adaptive radiation. The genetic regions controlling such patterns are "hotspots" for adaptive evolution, with small regions of the genome controlling major changes in wing pattern. Across multiple hybrid zones in Heliconius melpomene and related species, we no find no strong population signal of recent selection. Nonetheless, we find significant associations between genetic variation and wing pattern at multiple sites. This suggests patterning alleles are relatively old, and might be a better model for most natural adaptation, in contrast to the simple genetic basis of recent human-induced selection such as pesticide resistance. Strikingly, across the region controlling the red forewing band, a very strong association with phenotype implicates three genes as potentially being involved in control of wing pattern. One of these, a kinesin gene, shows parallel differences in expression levels between divergent forms in the two mimetic species, making it a strong candidate for control of wing pattern. These results show that mimicry involves parallel changes in gene expression and strongly suggest a role for this gene in control of wing pattern.

Genomic Hotspots for Adaptation: The Population Genetics of Mullerian Mimicry in Heliconius erato:
Identifying the genetic changes responsible for beneficial variation is essential for understanding how organisms adapt. Here, we use a combination of mapping, population genetic analysis, and gene expression studies to identify the genomic regions responsible for phenotypic evolution in the Neotropical butterfly Heliconius erato. H. erato, together with its co-mimic H. melpomene, have undergone parallel and concordant radiations in their warningly colored wing patterns across Central and South America. The "genes" underlying the H. erato color pattern radiation are classic examples of Mendelian loci of large effect and are under strong natural selection. Nonetheless, we do not see a clear molecular signal of recent natural selection, suggesting that the H. erato color pattern radiation, or the alleles that underlie it, may be quite old. Moreover, rather than being single locus, the genetic patterns suggest that multiple, widely dispersed loci may underlie pattern variation in H. erato. One of these loci, a kinesin gene, shows parallel expression differences between races during wing pattern formation in both H. erato and H. melpomene, suggesting that it plays an important role in pattern variation. High rates of recombination within naturally occurring H. erato hybrid zones mean that finer genetic dissection will allow us to localize causative sites and better understand the history and molecular basis of this extraordinary adaptive radiation.

Here's a section from the first paper which I found intriguing:
The results therefore appear to support the 'shifting balance' model for the evolution of Heliconius colour pattern races...whereby novel wing patterns arise and spread through otherwise continuous populations behind moving hybrid zones...The 'Pleistocene refuge' model seems less likely, as recent contact after extended periods of geographic isolation would presumably have left a stronger signal of genetic differentiation between divergent races, perhaps across the genome but especially more strongly in regions linked to patterning loci...

I have no idea why they necessarily think this validates the shifting balance. You can see David's critique of the model, but reading Will Provine's intellectual biography of Sewall Wright it seems that the shifting balance sometimes becomes the evolutionary genetic version of "it's complicated."* What they seem to have done here though is refute a simple model of powerful selective sweeps giving rise to these morphs recently. Rather, these seem to be ancient local adaptations, whose frequencies and genetic architectures are perhaps perturbed by long term exogenous (e.g., environment) and endogenous (e.g., complex frequency dependencies) dynamics.

Despite my lack of clarity on a few theoretical issues, I found the papers very interesting, and haven't really processed them fully.


Baxter SW, Nadeau NJ, Maroja LS, Wilkinson P, Counterman BA, et al. 2010 Genomic Hotspots for Adaptation: The Population Genetics of Mullerian Mimicry in the Heliconius melpomene Clade. PLoS Genet 6(2): e1000794. doi:10.1371/journal.pgen.1000794

Counterman BA, Araujo-Perez F, Hines HM, Baxter SW, Morrison CM, et al. 2010 Genomic Hotspots for Adaptation: The Population Genetics of Mullerian Mimicry in Heliconius erato. PLoS Genet 6(2): e1000796. doi:10.1371/journal.pgen.1000796

* I see one reference to epistasis in both papers, and that concept is very important in the shifting balance. Though I assume the LD and supergenes might point to that.


Eliezer Yudkowsky & Razib Khan on   posted by Razib @ 2/06/2010 12:52:00 AM


Friday, February 05, 2010

Hayek vs. Keynes   posted by Razib @ 2/05/2010 05:59:00 PM

You've probably watched the Hayek vs. Keynes rap by now:

Am the only one who was a little weirded out by the incongruity of John Maynard Keynes kickin' it with the honeys in the back of the limo? It isn't as if he was exactly on the down-low. He was a freak, swinging both ways, though not symmetrically....

Language goes extinct, human race to follow....   posted by Razib @ 2/05/2010 09:23:00 AM

Last speaker of ancient language of Bo dies in India:
Professor Anvita Abbi said that the death of Boa Sr was highly significant because one of the world's oldest languages - Bo - had come to an end.


"It is generally believed that all Andamanese languages might be the last representatives of those languages which go back to pre-Neolithic times," Professor Abbi said.

"The Andamanese are believed to be among our earliest ancestors."

I have a tendency to eye roll when people come out with these weepy stories about dying languages. When a language dies a people dies, more or less. No doubt there are particular stories, memories passed down which maintain continuity of identity, which disappear. But humans do not necessarily die. If members of obscure tribe X all learn English, or Chinese, tribe X as tribe X disappears, more or less. This is not trivial, I believe most humans would prefer that the cultural forms which pervade their own lives would pass down to future generations. Memory is to a great extent the only form of immortality we've had access to. But for members of obscure tribe X learning a widely spoken language is often a boon, and brings great benefit as they can engage in more fruitful exchanges with the broader human race. The implicit contract that peoples make with their own ancestors extracts too high a cost at some point, and when the present ceases to uphold its pact with the past, the past becomes obscured in the mists.

On a specific note about this article, the Andaman Islanders are actually a real concrete human population, they're not "among our earliest ancestors." Additionally, I thought that languages which were purely oral tended evolve faster than languages which were written down. Is it then plausible to make great claims for Bo's antiquity?

Related: The tragedy of dying languages. Larded with specious banalities or outright falsities, but good for a laugh.

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Ibn Khaldun In Our Time   posted by Razib @ 2/05/2010 01:09:00 AM

Ibn Khaldun on In Our Time. Excellent program. Khaldun's assessment that the Mamluks of Egypt had developed a system of rule which was robust against the decay of asabiyyah was born out by 450 years of subsequent history (that is, until the liquidation of the Mamluk ruling caste of Egypt in the 19th century). Unfortunately, the pervasive Islamic system of channeling slaves into the military and bureaucracy from the time of Al-Mu'tasim in the early 9th century seems to have been a local optimum. Like a Confucian bureaucratic state it was relatively stable and robust, maintaining a modicum of peace and order, but over the long term it produced stasis. These are social systems geared toward squeezing more "efficiencies" (operationally, rents for the elite) out of the system, not reinventing it so as to generate growth in wealth which compounds.

Monday, February 01, 2010

"Synthetic associations" and sickle cell anemia   posted by p-ter @ 2/01/2010 07:40:00 PM

Last week, I made a silly error in describing a problem in the sickle cell anemia example given by Dickson et al. (2010) as an empirical example of the phenomenon they call "synthetic association". So allow me to take a mulligan, and re-try this:

The authors performed an association study in African-Americans, using ~200 individuals with sickle cell anemia as cases, and >7,000 controls. From their description, they simply performed a logistic regression of disease status on common polymorphisms genome-wide. This turned up a large (~2.5Mb) region surrounding HBB (known to harbour the rare disease-causing mutation) as highly associated with the phenotype. This large region of association stands in contrast, they argue, to the known patterns of linkage disequilibrium in the region, which extends over a few kilobases at most.

This observation, they argue, is an empirical example of how associations due to rare variants can lead to large blocks of associations at common variants. This effect is due to the fact that haplotypes surrounding rare variants are longer and have had little time to be broken up by recombination. Under certain genetic models, this effect of "synthetic associations" is plausible, however, this example is a poor one for making their case.

The reason is that individuals with sickle cell anemia have two chromosomes of African ancestry in the region of HBB, while individuals without sickle cell anemia have approximately the background distribution of European and African chromosomes at the locus--~20% European and ~80% African. To put it another way, let X_d be number of chromosomes of African ancestry of an individual some distance d from HBB (X can be 0, 1, or 2), and Y be the number of chromosomes of African ancestry of an individual at HBB. In the cases, they've conditioned on the fact that Y=2, while in the controls they have not. P(X_d) != P(X_d | Y =2), so much of their association is likely due simply to differences in ancestry between the cases and controls in the HBB region (recall that admixture linkage disequilibrium in African-Americans extends for megabases).

More concretely, any SNP near the HBB locus that happened to be fixed for opposite alleles in Europe and Africa would have a whopping 20% allele frequency difference between cases and controls in their analysis, attributable simply to differences in local ancestry. That's the extreme (and unlikely) situation, but alleles with more modest allele frequency differences between populations will show the same effect.

To some extent, this is their point--the haplotype carrying the causal mutation is long. But the effect in this case is massively exaggerated by admixture, and the presentation of this exaggerated effect is misleading.


Half Sigma's flawed post on DTNBP1   posted by ben g @ 2/01/2010 10:33:00 AM

A while back, Mark and I were working on a comprehensive post which would try to tally the results of the various IQ-gene studies to see what they said about racial differences. We began this quest bright-eyed and hopeful that we would help contribute to ending a calamitous debate that has gone on for way too long. However, as we learned more about genetics, and these studies in particular, we came to realize that it's too early to take IQ-genes seriously.

We began with an approach similar to what Half Sigma did 2 years ago with the DTNBP1 gene. However, we soon learned that this approach was incredibly flawed and misleading. I wasn't going to write this post, but recently Half Sigma's DTBP1 post was linked from Reddit and tens of thousands of people are viewing it. When I saw that, I frustratedly criticized HS. He responded that I should give a more diplomatic and reasoned response, so here it is:

  1. You cannot simply add up SNPs from the same gene or chromosome. Half Sigma simply adds the observed effects of the SNPs to one another, ignoring that the alleles are highly correlated with one another, and not independently inherited, which is referred to as linkage disequilibrium (LD). The study that Half Sigma used provides the following table of LD for its SNPs:


    As can be seen in this table, pairwise LD goes as high as 1.0, meaning that two of the alleles are always inherited together. Adding these SNP's together is therefore like counting them twice.

  2. Group comparisons require replication in both groups. Because different populations have systematic genetic and environmental differences, an effect in one group may not occur in another. The study that Half Sigma uses relies primarily on a (small) sample of Dutch people. It is unclear whether these effects would exist in a population of African ancestry, let alone another European one.

  3. Candidate-gene association studies are not reliable. This is the most important point. Candidate gene association studies have largely failed to replicate. In fact, there have been no common IQ polymorphisms which have been replicated. Genome-wide association studies, which don't suffer as severely the various biases of candidate-gene association studies like publication bias or the winner's curse have not shown common SNP-associations with IQ.

    IQ is highly heritable, so the problem is the current methods, not the search for genes. With the development of sequencing technology and huge cohorts, we will be able to see the genes that are really behind normal IQ variation. With replication in multiple ethnicities and races, we will also see to what extent various genes and environments are responsible for group differences. There's no need to make proclamations of victory for hereditarianism or environmentalism in the mean time.

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